Glucocorticoids decrease the synthesis of type I procollagen mRNAs

Abstract

Glucocorticoids selectively decrease procollagen synthesis in animal and human skin fibroblasts. beta-Actin content and beta-actin mRNA are not affected by glucocorticoid treatment of chick skin fibroblasts. The inhibitory effect of glucocorticoids on procollagen synthesis is associated with a decrease in total cellular type I procollagen mRNAs in chick skin fibroblasts. These effects of dexamethasone are receptor mediated as determined by pretreatment with the glucocorticoid antagonists progesterone and RU-486 and with the agonist beta-dihydrocortisol. Dexamethasone has a small but significant inhibitory effect on cell growth of chick skin fibroblasts. The ability of this corticosteroid to decrease the steady-state levels of type I procollagen mRNAs in nuclei, cytoplasm, and polysomes varies. The largest decrease of type I procollagen mRNAs is observed in the nuclear and cytoplasmic subcellular fractions 24 h after dexamethasone treatment. Type I procollagen hnRNAs are also decreased as determined by Northern blot analysis of total nuclear RNA. The synthesis of total cellular type I procollagen mRNAs is reversibly decreased by dexamethasone treatment. In addition the synthesis of total nuclear type I procollagen mRNA sequences is decreased at 2, 4, and 24 h following the addition of radioactive nucleoside and dexamethasone to cell cultures. Although the synthesis of pro alpha 1(I) and pro alpha 2(I) mRNAs is decreased in dexamethasone-treated chick skin fibroblasts, the degradation of the total cellular procollagen mRNAs is not altered while the degradation of total cellular RNA is stabilized. These data indicate that the dexamethasone-mediated decrease of procollagen synthesis in embryonic chick skin fibroblasts results from the regulation of procollagen gene expression.

Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity

“…In vitro experiments have demonstrated that DEX is able to reduce collagen synthesis by fibroblasts [30,31]. In line with this, DEX treatment has been demonstrated to decrease total body collagen synthesis in infants with CLD [9,32].…”

Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA.

“…In contrast, glucocorticoids decrease transcription of the genes for proopiomelacortin in pituitary tumor cells (29), a1-fetoprotein in developing rat liver cells (30), type 1 procollagen in chicken skin fibroblasts (31), and collagenase in rabbit synovial cells (24). During the shutdown of transcription by glucocorticoid hormones, there is no demonstrably accelerated breakdown of nascent transcripts (24,30,31). In contrast, Dex does not influence transcription of f3-actin or FOS genes or the stability of the corresponding mRNAs in U-937 cells.…”

Transdifferentiation-dependent expression of α-SMA in hepatic stellate cells does not involve TGF-β pathways leading to coinduction of collagen type I and thrombospondin-2

“…The synthetic glucocorticoid dexamethasone was previously described to antagonize TGF-h effects, especially collagen inducing properties (Gras et al, 2001;Cockayne et al, 1986) and it was recently demonstrated in HSC that glucocorticoids reduce the bioavailability of TGF-h directly (Bolkenius et al, 2004).…”